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Esophagus 3.1.1.2
+ Data elements preceded by this symbol are not required. However, these elements may be
clinically important but are not yet validated or regularly used in patient management.
CAP Approved
Esophagus 3.1.1.2
+ Data elements preceded by this symbol are not required. However, these elements may be
clinically important but are not yet validated or regularly used in patient management.
CAP Approved
Esophagus 3.1.1.2
Distal Margin
___ Cannot be assessed
___ Uninvolved by invasive carcinoma or dysplasia
___ Involved by invasive carcinoma
___ Involved by dysplasia
___ Squamous dysplasia
___ Low grade
___ High grade
___ Intestinal metaplasia (Barretts esophagus) with dysplasia
___ Low grade
___ High grade
___ Involved by intestinal metaplasia (Barretts esophagus) without dysplasia
Circumferential (Adventitial) Margin (esophagectomy or esophagogastrectomy specimens) or
Deep Margin (endoscopic resection specimens)
___ Cannot be assessed
___ Uninvolved by invasive carcinoma
___ Involved by invasive carcinoma
Other Margin(s) (required only if applicable)
Specify margin(s): ___________________________
___ Cannot be assessed
___ Uninvolved by invasive carcinoma
___ Involved by invasive carcinoma
Treatment Effect (applicable to carcinomas treated with neoadjuvant therapy) (select all that apply)
(Note G)
___ No prior treatment
___ Present
+ ___ No residual tumor (complete response, grade 0)
+ ___ Marked response (grade 1, minimal residual cancer)
+ ___ Moderate response (grade 2)
___ No definite response identified (grade 3, poor or no response)
___ Treatment history not known
Lymph-Vascular Invasion
___ Not identified
___ Present
___ Indeterminate
+ Perineural Invasion
+ ___ Not identified
+ ___ Present
+ ___ Indeterminate
Pathologic Staging (pTNM) (Note H)
TNM Descriptors (required only if applicable) (select all that apply)
___ m (multiple primary tumors)
___ r (recurrent)
___ y (posttreatment)
+ Data elements preceded by this symbol are not required. However, these elements may be
clinically important but are not yet validated or regularly used in patient management.
CAP Approved
Esophagus 3.1.1.2
+ Data elements preceded by this symbol are not required. However, these elements may be
clinically important but are not yet validated or regularly used in patient management.
CAP Approved
Esophagus 3.1.1.2
+ Data elements preceded by this symbol are not required. However, these elements may be
clinically important but are not yet validated or regularly used in patient management.
Background Documentation
Esophagus 3.1.1.2
Explanatory Notes
A. Application
This protocol applies to all carcinomas arising in the esophagus and to carcinomas involving the
esophagogastric junction (EGJ), including tumors that cross the EGJ but are predominantly located in
the proximal stomach. Lymphomas, well-differentiated neuroendocrine tumors (carcinoid tumors), and
sarcomas are also not included (separate TNM staging systems1 and CAP protocols apply).
B. Location
The location of the tumor in the esophagus (cervical, upper thoracic, midthoracic, lower thoracic,
abdominal) and with respect to the macroscopic EGJ (defined as where the tubular esophagus meets
the stomach, as measured from the top of the gastric folds) should be noted whenever possible (Figure
1). The macroscopic EGJ often does not correspond to the junction of esophageal squamous mucosa
and columnar mucosa because of the common finding in esophageal resection specimens of
glandular mucosa involving the distal esophagus. Because anatomic divisions of the esophagus are
defined by anatomic boundaries and relationships to other structures,1 it may not be possible for the
pathologist to determine exact tumor location from the resection specimen.
Figure 1. Anatomic subdivisions of the esophagus. From Edge et al.1 Used with permission of the American Joint
Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging
Manual, 7th edition (2009) published by Springer Science and Business Media LLC, www.springerlink.com.
For tumors involving the esophagogastric junction, specific observations should be recorded in an
attempt to establish the exact site of origin of the tumor. The EGJ is defined as the junction of the tubular
esophagus and the stomach, irrespective of the type of epithelial lining of the esophagus.
The pathologist should record the maximum longitudinal dimension of the tumor mass, the distance of
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Background Documentation
Esophagus 3.1.1.2
the tumor midpoint from the EGJ, and the relative proportions of the tumor mass located in the
esophagus and in the stomach.
Tumors involving the EGJ are classified for purposes of staging as esophageal carcinomas.1 Although
the nature of these tumors (gastric versus esophageal) has been controversial2,3 (reviewed by Carneiro
and Chaves4), recent data support their classification as esophageal carcinomas.1 The World Health
Organization (WHO) defines esophageal tumors are those located entirely above the EGJ and proximal
gastric tumors as those located entirely below the EGJ.5 Tumors crossing the EGJ are classified as EGJ
tumors. An alternative system proposed by Siewart and colleagues divides adenocarcinomas involving
the EGJ into three categories, based upon location of the midpoint of the tumor6:
Type I: adenocarcinoma of the distal esophagus, with or without infiltration of the EGJ from above
Type II: true carcinoma of the gastric cardia, arising from the cardiac epithelium or short segments with
intestinal metaplasia at the EGJ
Type III: subcardial gastric carcinoma, which infiltrates the EGJ and distal esophagus from below
Application of the Siewart system is complicated by lack of consensus as to the definition and nature of
the gastric cardia, with some investigators regarding it as a normal anatomic finding,7 and others as a
metaplastic response to injury from esophagogastric reflux.2,4
C. Histologic Type
For consistency in reporting, the histologic classification proposed by the WHO is recommended.5
However, this protocol does not preclude the use of other systems of classification or histologic types.
Worldwide, squamous cell carcinoma continues to predominant as the most common histologic type,
but numerous population-based studies document the increasing incidence of adenocarcinoma of the
esophagus and EGJ in Western countries.8 More than 50% of esophageal carcinomas diagnosed in the
United States since 1900 are adenocarcinomas. Other subtypes, such as adenoid cystic carcinoma
and mucoepidermoid carcinoma, which resemble their counterparts arising in salivary gland, are rarely
encountered.
The revised TNM staging system for esophageal carcinomas incorporates tumor grade and
histologic type in the stage groupings (see Note H). Mixed histologic types, such as
adenosquamous carcinomas, are staged using the squamous cell carcinoma stage
grouping.1
WHO Classification of Carcinoma of the Esophagus
Squamous cell carcinoma
Verrucous (squamous) carcinoma
Spindle cell (squamous) carcinoma
Adenocarcinoma
Adenosquamous carcinoma
Mucoepidermoid carcinoma#
Adenoid cystic carcinoma#
High-grade neuroendocrine carcinoma
Large cell neuroendocrine carcinoma
Small cell neuroendocrine carcinoma#
Undifferentiated carcinoma#
Others
#These
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Esophagus 3.1.1.2
The term carcinoma, NOS (not otherwise specified) is not part of the WHO classification.
D. Histologic Grade
The histologic grades for esophageal squamous cell carcinomas are as follows:
Grade X
Grade 1
Grade 2
Grade 3
If there are variations in the differentiation within the tumor, the highest (least favorable) grade is
recorded. In general, mucoepidermoid carcinoma and adenoid cystic carcinoma of the esophagus
are not amenable to grading.
For adenocarcinomas, a suggested grading system based on the proportion of the tumor that is
composed of glands is as follows:
Grade X
Grade 1
Grade 2
Grade 3
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Background Documentation
Esophagus 3.1.1.2
Figure 2. Microscopic anatomy of the esophagus. From Edge et al.1 Used with permission of the American Joint
Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging
Manual, 7th edition (2009) published by Springer Science and Business Media LLC, www.springerlink.com.
F. Margins
Margins include the proximal, distal, and radial margins. The radial margin represents the adventitial soft
tissue margin closest to the deepest penetration of tumor. Sections to evaluate the proximal and distal
resections margins can be obtained in 2 orientations: (1) en face sections parallel to the margin, or
(2) longitudinal sections perpendicular to the margin. Depending on the closeness of the tumor to the
margin, select the orientation(s) that will most clearly demonstrate the status of the margin. The distance
from the tumor edge to the closest resection margin(s) should be measured. Proximal and distal
resection margins should be evaluated for Barretts esophagus and for squamous and glandular
dysplasia. It may be helpful to mark the margin(s) closest to the tumor with ink. Margins marked by ink
should be so designated in the macroscopic description.
G. Treatment Effect
Response of tumor to previous chemotherapy or radiation therapy should be reported.
Although grading systems for tumor response have not been established, in general, three-category
systems provide good interobserver reproducibility.11 The following system is suggested:
Description
0 (Complete response)
1 (Moderate response)
2 (Minimal response)
3 (Poor response)
Sizable pools of acellular mucin may be present after chemoradiation but should not be interpreted as
representing residual tumor.
This protocol does not preclude the use of other systems for assessment of tumor response.12-14
H. TNM and Anatomic Stage/Prognostic Groupings
The TNM staging system for esophageal carcinoma of the American Joint Committee on Cancer
(AJCC) and the International Union Against Cancer (UICC) is recommended (Figure 3).1
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Background Documentation
Esophagus 3.1.1.2
Figure 3. T, N, and M classifications for esophageal carcinoma. From Edge et al.1 Used with permission of the
American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC
Cancer Staging Manual, 7th edition (2009) published by Springer Science and Business Media LLC,
www.springerlink.com.
According to AJCC/UICC convention, the designation T refers to a primary tumor that has not been
previously treated. The symbol p refers to the pathologic classification of the TNM, as opposed to the
clinical classification, and is based on gross and microscopic examination. pT entails a resection of the
primary tumor or biopsy adequate to evaluate the highest pT category, pN entails removal of nodes
adequate to validate lymph node metastasis, and pM implies microscopic examination of distant
lesions. Clinical classification (cTNM) is usually carried out by the referring physician before treatment
during initial evaluation of the patient or when pathologic classification is not possible.
Pathologic staging is usually performed after surgical resection of the primary tumor. Pathologic staging
depends on pathologic documentation of the anatomic extent of disease, whether or not the primary
tumor has been completely removed. If a biopsied tumor is not resected for any reason (eg, when
technically infeasible) and if the highest T and N categories or the M1 category of the tumor can be
confirmed microscopically, the criteria for pathologic classification and staging have been satisfied
without total removal of the primary cancer.
TNM Descriptors
For identification of special cases of TNM or pTNM classifications, the m suffix and y, r, and a
prefixes are used. Although they do not affect the stage grouping, they indicate cases needing
separate analysis.
The m suffix indicates the presence of multiple primary tumors in a single site and is recorded in
parentheses: pT(m)NM.
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Background Documentation
Esophagus 3.1.1.2
The y prefix indicates those cases in which classification is performed during or after initial
multimodality therapy (ie, neoadjuvant chemotherapy, radiation therapy, or both chemotherapy and
radiation therapy). The cTNM or pTNM category is identified by a y prefix. The ycTNM or ypTNM
categorizes the extent of tumor actually present at the time of that examination. The y categorization
is not an estimate of tumor before multimodality therapy (ie, before initiation of neoadjuvant therapy).
The r prefix indicates a recurrent tumor when staged after a documented disease-free interval and is
identified by the r prefix: rTNM.
The a prefix designates the stage determined at autopsy: aTNM.
N Category Considerations
A mediastinal lymphadenectomy specimen will ordinarily include 7 or more regional lymph nodes.
Stage Groupings: Squamous Cell Carcinoma
Stage
T
N
M
Stage 0
Tis
N0
M0 #
Stage IA
T1
N0
M0
Stage IB
T1
N0
M0
T2 or T3
N0
M0
Stage IIA
T2 or T3
N0
M0
T2 or T3
N0
M0
Stage IIB
T2 or T3
N0
M0
T1 or T2
N1
M0
Stage IIIA
T1 or T2
N2
M0
T3
N1
M0
T4a
N0
M0
Stage IIIB
T3
N2
M0
Stage IIIC
T4a
N1 or N2
M0
T4b
Any
M0
Any
N3
M0
Stage IV
Any T
Any N
M1
#
G
1
1
2 or 3
1
1
2 or 3
2 or 3
Any
Any
Any
Any
Any
Any
Any
Any
Any
Location
Any
Any
Any
Lower
Upper, middle
Lower
Upper, middle
Any
Any
Any
Any
Any
Any
Any
Any
Any
M
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
G
1
1 or 2
3
1 to 2
3
Any
Any
Any
Any
Any
Any
Any
Any
Any
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Background Documentation
Stage IV
#
Any T
Any N
Esophagus 3.1.1.2
M1
Any
Additional Descriptors
Lymph-Vascular Invasion
Lymph-vascular invasion (LVI) indicates whether microscopic lymph-vascular invasion is identified in the
pathology report. LVI includes lymphatic invasion, vascular invasion, or lymph-vascular invasion. By
AJCC/UICC convention, LVI does not affect the T category indicating local extent of tumor unless
specifically included in the definition of a T category.
I. Regional Lymph Nodes
Regional lymph nodes (Figure 4) extend from periesophageal cervical nodes for the cervical esophagus
to celiac lymph nodes for the distal esophagus.1 Number of involved lymph nodes has consistently
emerged as a prognostic indicator on multivariate analysis.15,16 Extranodal extension may identify a
subset of node-positive patients with a particularly poor prognosis.17
Figure 4. Regional lymph nodes of the esophagus. From Edge et al.1 Used with permission of the American Joint
Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging
Manual, 7th edition (2009) published by Springer Science and Business Media LLC, www.springerlink.com.
J. Additional Findings
Most esophageal adenocarcinomas develop in the setting of Barretts esophagus, which is defined as
alteration of the mucosal lining of the esophagus from the normal squamous epithelium to metaplastic
columnar epithelium in response to esophagogastric reflux. Although in some cases the columnar
epithelium may resemble gastric oxyntic or cardiac mucosa, only the specialized columnar epithelium
with goblet cells is considered to carry significant risk of cancer and is designated as Barretts
esophagus for diagnostic purposes.
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